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    In Vivo Brain Delivery and Brain Deposition of Proteins with Various Sizes

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    Issue Date
    2019-10-30
    Author
    Ulapane, Kavisha R.
    Kopec, Brian M.
    Siahaan, Teruna J.
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2019 American Chemical Society.
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    Abstract
    It is very challenging to develop protein drugs for the treatment of brain diseases; this is due to the difficulty in delivering them into the brain because of the blood–brain barrier (BBB). Thus, alternative delivery methods need further exploration for brain delivery of proteins to diagnose and treat brain diseases. Previously, ADTC5 and HAV6 peptides have been shown to enhance the in vivo brain delivery of small- and medium-size molecules across the BBB. This study was carried out to evaluate the ability of ADTC5 and HAV6 peptides to enhance delivery of proteins of various sizes, such as 15 kDa lysozyme, 65 kDa albumin, 150 kDa IgG mAb, and 220 kDa fibronectin, into the brains of C57BL/6 mice. Each protein was labeled with IRdye800CW, and a quantitative method using near IR fluorescence (NIRF) imaging was developed to determine the amount of protein delivered into the brain. ADTC5 peptide significantly enhanced brain delivery of lysozyme, albumin, and IgG mAb but not fibronectin compared to controls. In contrast, HAV6 peptide significantly enhanced the brain delivery of lysozyme but not albumin and IgG mAb. Thus, there is a cutoff size of proteins that can be delivered by each peptide. The distribution of delivered protein in other organs such as liver, spleen, lung, kidney, and heart could be influenced by HAV6 and ADTC5. In summary, ADTC5 is a better BBB modulator than HAV6 in delivering various sizes of proteins into the brain, and the size of the protein affects its brain delivery.
    Description
    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.9b00763.
    URI
    http://hdl.handle.net/1808/32231
    DOI
    https://doi.org/10.1021/acs.molpharmaceut.9b00763
    Collections
    • Pharmaceutical Chemistry Scholarly Works [336]
    Citation
    Ulapane, K. R., Kopec, B. M., & Siahaan, T. J. (2019). In Vivo Brain Delivery and Brain Deposition of Proteins with Various Sizes. Molecular pharmaceutics, 16(12), 4878–4889. https://doi.org/10.1021/acs.molpharmaceut.9b00763

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    KU Libraries
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    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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